The invention relates to cell growth regulatory proteins.
Mammalian transcription factors regulate cellular processes such as cell lineage determination, cell growth and differentiation, and temporal or cell type-specific gene expression (Maniatis et al., 1987, Science 236:1237-1245; Mitchell et al., 1989, Science 245:371-378; Ptashne et al., 1990, Nature 346:329-331). Upon binding to specific cis-acting DNA sequences, transcription factors activate or repress transcription (Johnson, 1995, Cell 81:655-658; Tjian et al., 1994, Cell 77:5-8). Transcription factors are typically classified according to their DNA binding domains such as helix-loop-helix, leucine zipper, homeodomain, and zinc finger. The zinc finger transcription factors can be further classified into subfamilies based on amino acids important for zinc binding (e.g., Cys2His2, Cys4, or Cys3His1), spacing between the zinc binding amino acids, and transcription activation or repression domain (e.g., glutamine rich, acidic amino acid rich, or proline rich domain).
The erythroid Kruppel-like factor (EKLF) subfamily includes zinc finger proteins, such as erythroid (EKLF) and lung (LKLF) Kruppel-like factors, and BTEB2 (or placental Kruppel-like factor). These proteins are preferentially expressed in certain mammalian tissues, where they transactivate gene expression upon binding to DNA. This subfamily is characterized by a highly conserved C-terminal region (more than 80% conserved) containing three Cys2His2 zinc fingers and a proline rich N-terminal domain (Anderson et al., 1995, Mol. Cell. Biol. 15:5957-5965; Donze et al., 1995, J. Biol. Chem. 270:1955-1959; Miller et al., 1993, Mol. Cell. Biol. 13:2776-2786; Sogawa et al., 1993, Nucl. Acids Res. 21:1527-1532). EKLF is essential for the expression of the .beta.-globin gene in mice. The zinc fingers of EKLF bind a CACCC regulatory element of the .beta.-globin promoter.